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Translational Neurodegeneration
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Open Access 01-12-2017 | Research

Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating HSP70 in SHSY-5Y cells

Authors: Hui Sun, Ming Jiang, Xing Fu, Qiong Cai, Jingxing Zhang, Yanxin Yin, Jia Guo, Lihua Yu, Yun Jiang, Yigang Liu, Liang Feng, Zhiyu Nie, Jianmin Fang, Lingjing Jin

Published in: Translational Neurodegeneration | Issue 1/2017

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Abstract

Background

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress (ER stress). HSP70 family, a chaperon like heat shock protein family, was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells. However, the ER stress relative transcriptome, in MANF signaling cascades is still investigated. The involvement of HSP70, a 70kd member of HSP70 family, need further to be verified.

Methods

The cell apoptosis was assayed by MTT, TUNEL staining and western blot of cleaved Caspase-3. The differentially expressed genes in SHSY-5Y cells under different conditions (control, 6-OHDA, 6-OHDA + MANF) were investigated by RNA-seq. Expression of HSP70 was further confirmed by real-time PCR. RNAi knockdown for HSP70 was performed to investigate the role of HSP70 in the MANF signaling pathway.

Results

MANF inhibits 6-OHDA-induced apoptosis in SHSY-5Y cells. Six ER stress relative genes (HSP70, GRP78, xbp-1, ATF-4, ATF-6, MAPK) were found enriched in 6-OHDA + MANF treatment group. HSP70 was the most significantly up-regulated gene under 6-OHDA + MANF treatment in SHSY-5Y cells. RNAi knockdown for HSP70 inhibits the protective effects of MANF against 6-OHDA toxicity in SHSY-5Y cells.

Conclusion

MANF exerts a protective role against 6-OHDA induced apoptosis in SHSY-5Y cells via up-regulating some ER stress genes, including HSP70 family members. The HSP70 expression level plays a key role in MANF-mediated survival pathway.
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Metadata
Title
Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating HSP70 in SHSY-5Y cells
Authors
Hui Sun
Ming Jiang
Xing Fu
Qiong Cai
Jingxing Zhang
Yanxin Yin
Jia Guo
Lihua Yu
Yun Jiang
Yigang Liu
Liang Feng
Zhiyu Nie
Jianmin Fang
Lingjing Jin
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Translational Neurodegeneration / Issue 1/2017
Electronic ISSN: 2047-9158
DOI
https://doi.org/10.1186/s40035-017-0082-8

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